Mouse natural killer (NK) cells and natural cytotoxic (NC) cells have been shown to be closely associated with large granular lymphocytes (LGL), as has been found previously for man and rats. In in vivo studies, natural effector cells reacting with certain solid tumors were found to share some characteristics of both NK and NC cells. Natural effector cells with the characteristics of NK cells, in both mice and humans, were found to frequently be reactive against primary carcinomas, and such reactivity was augmented by interferon (IFN) and by interleukin-2 (IL-2). Detailed studies have been performed on the conditions for in vitro growth and differentiation of mouse and human NK cells, using limiting dilution assays. IL-2 was shown to be an important stimulus for both growth and activity of NK cells, and IFN was shown to be able to both stimulate and inhibit in vitro growth of NK cells, depending on culture conditions. Negative regulation of NK activity has been studied, with emphasis on the nature of suppressor cells and the mechanism of inhibition by prostaglandins. Increased evidence has been obtained for an in vivo role of NK cells, in resistance against metastases and in immune surveillance.